High-resolution fMRI Research Articles

Haptic fMRI: Reliability and performance of electromagnetic haptic interfaces for motion and force neuroimaging experiments.

Haptic interfaces compatible with functional magnetic resonance imaging (Haptic fMRI) promise to enable rich motor neuroscience experiments that study how humans perform complex manipulation tasks. Here, we present a large-scale study (176 scans runs, 33 scan sessions) that characterizes the reliability and performance of one such electromagnetically actuated device, Haptic fMRI Interface 3 (HFI-3). We outline engineering advances that ensured HFI-3 did not interfere with fMRI measurements. Observed fMRI temporal noise levels with HFI-3 operating were at the fMRI baseline (0.8% noise to signal). We also present results from HFI-3 experiments demonstrating that high resolution fMRI can be used to study spatio-temporal patterns of fMRI blood oxygenation dependent (BOLD) activation. These experiments include motor planning, goal-directed reaching, and visually-guided force control. Observed fMRI responses are consistent with existing literature, which supports Haptic fMRI's effectiveness at studying the brain's motor regions.

A proof-of-concept study for developing integrated two-photon microscopic and magnetic resonance imaging modality at ultrahigh field of 16.4 tesla

Functional magnetic resonance imaging (fMRI) based on the blood oxygen level dependent (BOLD) contrast has gained a prominent position in neuroscience for imaging neuronal activity and studying effective brain connectivity under working state and functional connectivity at resting state. However, the fundamental questions in regards to fMRI technology: how the BOLD signal inferences the underlying microscopic neuronal activity and physiological changes and what is the ultimate specificity of fMRI for functional mapping of microcircuits, remain unanswered. The capability of simultaneous fMRI measurement and functional microscopic imaging in a live brain thus holds the key to link the microscopic and mesoscopic neural dynamics to the macroscopic brain activity at the central nervous system level. Here we report the first demonstration to integrate high-resolution two-photon fluorescence microscopy (TPM) with a 16.4 tesla MRI system, which proves the concept and feasibility for performing simultaneous high-resolution fMRI and TPM imaging at ultrahigh magnetic field.

Association between habenula dysfunction and motivational symptoms in unmedicated major depressive disorder.

The lateral habenula plays a central role in reward and punishment processing and has been suggested to drive the cardinal symptom of anhedonia in depression. This hypothesis is largely based on observations of habenula hypermetabolism in animal models of depression, but the activity of habenula and its relationship with clinical symptoms in patients with depression remains unclear. High-resolution functional magnetic resonance imaging (fMRI) and computational modelling were used to investigate the activity of the habenula during a probabilistic reinforcement learning task with rewarding and punishing outcomes in 21 unmedicated patients with major depression and 17 healthy participants. High-resolution anatomical scans were also acquired to assess group differences in habenula volume. Healthy individuals displayed the expected activation in the left habenula during receipt of punishment and this pattern was confirmed in the computational analysis of prediction error processing. In depressed patients, there was a trend towards attenuated left habenula activation to punishment, while greater left habenula activation was associated with more severe depressive symptoms and anhedonia. We also identified greater habenula volume in patients with depression, which was associated with anhedonic symptoms. Habenula dysfunction may contribute to abnormal response to punishment in patients with depression, and symptoms such as anhedonia.

Emotional arousal impairs association-memory: Roles of amygdala and hippocampus

Emotional arousal is well-known to enhance memory for individual items or events, whereas it can impair association memory. The neural mechanism of this association memory impairment by emotion is not known: In response to emotionally arousing information, amygdala activity may interfere with hippocampal associative encoding (e.g., via prefrontal cortex). Alternatively, emotional information may be harder to unitize, resulting in reduced availability of extra-hippocampal medial temporal lobe support for emotional than neutral associations. To test these opposing hypotheses, we compared neural processes underlying successful and unsuccessful encoding of emotional and neutral associations. Participants intentionally studied pairs of neutral and negative pictures (Experiments 1–3). We found reduced association-memory for negative pictures in all experiments, accompanied by item-memory increases in Experiment 2. High-resolution fMRI (Experiment 3) indicated that reductions in associative encoding of emotional information are localizable to an area in ventral-lateral amygdala, driven by attentional/salience effects in the central amygdala. Hippocampal activity was similar during both pair types, but a left hippocampal cluster related to successful encoding was observed only for negative pairs. Extra-hippocampal associative memory processes (e.g., unitization) were more effective for neutral than emotional materials. Our findings suggest that reduced emotional association memory is accompanied by increases in activity and functional coupling within the amygdala. This did not disrupt hippocampal association-memory processes, which indeed were critical for successful emotional association memory formation.

Analysis strategies for high-resolution UHF-fMRI data

Functional MRI (fMRI) benefits from both increased sensitivity and specificity with increasing magnetic field strength, making it a key application for Ultra-High Field (UHF) MRI scanners. Most UHF-fMRI studies utilize the dramatic increases in sensitivity and specificity to acquire high-resolution data reaching sub-millimeter scales, which enable new classes of experiments to probe the functional organization of the human brain. This review article surveys advanced data analysis strategies developed for high-resolution fMRI at UHF. These include strategies designed to mitigate distortion and artifacts associated with higher fields in ways that attempt to preserve spatial resolution of the fMRI data, as well as recently introduced analysis techniques that are enabled by these extremely high-resolution data. Particular focus is placed on anatomically-informed analyses, including cortical surface-based analysis, which are powerful techniques that can guide each step of the analysis from preprocessing to statistical analysis to interpretation and visualization. New intracortical analysis techniques for laminar and columnar fMRI are also reviewed and discussed. Prospects for single-subject individualized analyses are also presented and discussed. Altogether, there are both specific challenges and opportunities presented by UHF-fMRI, and the use of proper analysis strategies can help these valuable data reach their full potential.

High-resolution functional MRI identified distinct global intrinsic functional networks of nociceptive posterior insula and S2 regions in squirrel monkey brain

Numerous functional imaging and electrophysiological studies in humans and animals indicate that the two contiguous areas of secondary somatosensory cortex (S2) and posterior insula (pIns) are core regions in nociceptive processing and pain perception. In this study, we tested the hypothesis that the S2-pIns connection serves as a hub for connecting distinct sensory and affective nociceptive processing networks in the squirrel monkey brain. At 9.4T, we first mapped the brain regions that respond to nociceptive heat stimuli with high-resolution fMRI, and then used seed-based resting-state fMRI (rsfMRI) analysis to delineate and refine the global intrinsic functional connectivity circuits of the proximal S2 and pIns regions. In each subject, nociceptive (47.5°C) heat-evoked fMRI activations were detected in many brain regions, including primary somatosensory (S1), S2, pIns, area 7b, anterior cingulate cortex (ACC), primary motor cortex, prefrontal cortex, supplementary motor area, thalamus, and caudate. Using the heat-evoked fMRI activation foci in S2 and pIns as the seeds, voxel-wise whole-brain resting-state functional connectivity (rsFC) analysis revealed strong functional connections between contralateral S2 and pIns, as well as their corresponding regions in the ipsilateral hemisphere. Spatial similarity and overlap analysis identified each region as part of two distinct intrinsic functional networks with 7% overlap: sensory S2-S1-area 7b and affective pIns-ACC-PCC networks. Moreover, a high degree of overlap was observed between the combined rsFC maps of nociceptive S2 and pIns regions and the nociceptive heat-evoked activation map. In summary, our study provides evidence for the existence of two distinct intrinsic functional networks for S2 and pIns nociceptive regions, and these two networks are joined via the S2-pIns connection. Brain regions that are involved in processing nociceptive inputs are also highly interconnected at rest. The presence of robust and distinct S1-S2-area 7b and pIns-ACC-PCC rsFC networks under anesthesia underscores their fundamental roles in processing nociceptive information.

Optimization of functional MRI for detection, decoding and high-resolution imaging of the response patterns of cortical columns

The capacity of functional MRI (fMRI) to resolve cortical columns depends on several factors. These include the spatial scale of the columnar pattern, the point-spread of the fMRI response, the voxel size, and the signal-to-noise ratio (SNR) considering thermal and physiological noise. However, it remains unknown how these factors combine, and what is the voxel size that optimizes fMRI of cortical columns.Here we combine current knowledge into a quantitative model of fMRI of realistic patterns of cortical columns with different spatial scales and degrees of irregularity. We compare different approaches for identifying patterns of cortical columns, including univariate and multivariate based detection, multi-voxel pattern analysis (MVPA) based decoding, and high-resolution imaging and reconstruction of the pattern of cortical columns. We present the dependence of the performance of each approach on the parameters of the imaged pattern as well as those of the data acquisition. In addition, we predict voxel sizes that optimize fMRI of cortical columns under various scenarios.We found that all measures associated with multivariate detection and decoding could be approximately calculated from a measure we termed “multivariate contrast-to-noise ratio” (mv-CNR), which is a function of the contrast-to-noise ratio (CNR) and number of voxels. Furthermore, mv-CNR implied that the optimal voxel width for detection and decoding is independent of changes in response amplitude, SNR and imaged volume that are not caused by changes in voxel size.For regular patterns, optimal voxel widths for detection, decoding and imaging/reconstructing the pattern of cortical columns were approximately half the main cycle length of the organization. Optimal voxel widths for irregular patterns were less dependent on the main cycle length, and differed between univariate detection, multivariate detection and decoding, and reconstruction. We compared the effects of different factors of Gradient Echo fMRI at 3 Tesla (T), Gradient Echo fMRI at 7T, and Spin-Echo fMRI at 7T on the detection, decoding, and reconstruction measures considered and found that in all cases the width of the fMRI point-spread had the most significant effect. In contrast, different response amplitudes and noise characteristics played a relatively minor role. We recommend specific voxel widths for optimal univariate detection, for multivariate detection and decoding, and for high-resolution imaging of cortical columns under these three data-acquisition scenarios. Our study supports the planning, optimization, and interpretation of high-resolution fMRI of cortical columns and the decoding of information conveyed by these columns.

Reconstructing the spectrotemporal modulations of real-life sounds from fMRI response patterns

Ethological views of brain functioning suggest that sound representations and computations in the auditory neural system are optimized finely to process and discriminate behaviorally relevant acoustic features and sounds (e.g., spectrotemporal modulations in the songs of zebra finches). Here, we show that modeling of neural sound representations in terms of frequency-specific spectrotemporal modulations enables accurate and specific reconstruction of real-life sounds from high-resolution functional magnetic resonance imaging (fMRI) response patterns in the human auditory cortex. Region-based analyses indicated that response patterns in separate portions of the auditory cortex are informative of distinctive sets of spectrotemporal modulations. Most relevantly, results revealed that in early auditory regions, and progressively more in surrounding regions, temporal modulations in a range relevant for speech analysis (∼2-4 Hz) were reconstructed more faithfully than other temporal modulations. In early auditory regions, this effect was frequency-dependent and only present for lower frequencies (<∼2 kHz), whereas for higher frequencies, reconstruction accuracy was higher for faster temporal modulations. Further analyses suggested that auditory cortical processing optimized for the fine-grained discrimination of speech and vocal sounds underlies this enhanced reconstruction accuracy. In sum, the present study introduces an approach to embed models of neural sound representations in the analysis of fMRI response patterns. Furthermore, it reveals that, in the human brain, even general purpose and fundamental neural processing mechanisms are shaped by the physical features of real-world stimuli that are most relevant for behavior (i.e., speech, voice).

Comparing functional MRI protocols for small, iron-rich basal ganglia nuclei such as the subthalamic nucleus at 7 T and 3 T.

The basal ganglia (BG) form a network of subcortical nuclei. Functional magnetic resonance imaging (fMRI) in the BG could provide insight in its functioning and the underlying mechanisms of Deep Brain Stimulation (DBS). However, fMRI of the BG with high specificity is challenging, because the nuclei are small and variable in their anatomical location. High resolution fMRI at field strengths of 7 Tesla (T) could help resolve these challenges to some extent. A set of MR protocols was developed for functional imaging of the BG nuclei at 3 T and 7 T. The protocols were validated using a stop-signal reaction task (Logan et al. []: J Exp Psychol: Human Percept Perform 10:276-291). Compared with sub-millimeter 7 T fMRI protocols aimed at cortex, a reduction of echo time and spatial resolution was strictly necessary to obtain robust Blood Oxygen Level Dependent (BOLD) sensitivity in the BG. An fMRI protocol at 3 T with identical resolution to the 7 T showed no robust BOLD sensitivity in any of the BG nuclei. The results suggest that the subthalamic nucleus, as well as the substantia nigra, red nucleus, and the internal and external parts of the globus pallidus show increased activation in failed stop trials compared with successful stop and go trials. Hum Brain Mapp 38:3226-3248, 2017. © 2017 Wiley Periodicals, Inc.

Not in one metric: Neuroticism modulates different resting state metrics within distinctive brain regions

IntroductionNeuroticism is a complex personality trait encompassing diverse aspects. Notably, high levels of neuroticism are related to the onset of psychiatric conditions, including anxiety and mood disorders. Personality traits are stable individual features; therefore, they can be expected to be associated with stable neurobiological features, including the Brain Resting State (RS) activity as measured by fMRI. Several metrics have been used to describe RS properties, yielding rather inconsistent results. This inconsistency could be due to the fact that different metrics portray different RS signal properties and that these properties may be differently affected by neuroticism. To explore the distinct effects of neuroticism, we assessed several distinct metrics portraying different RS properties within the same population. MethodNeuroticism was measured in 31 healthy subjects using the Zuckerman-Kuhlman Personality Questionnaire; RS was acquired by high-resolution fMRI. Using linear regression, we examined the modulatory effects of neuroticism on RS activity, as quantified by the Amplitude of low frequency fluctuations (ALFF, fALFF), regional homogeneity (REHO), Hurst Exponent (H), global connectivity (GC) and amygdalae functional connectivity. ResultsNeuroticism modulated the different metrics across a wide network of brain regions, including emotional regulatory, default mode and visual networks. Except for some similarities in key brain regions for emotional expression and regulation, neuroticism affected different metrics in different ways. DiscussionMetrics more related to the measurement of regional intrinsic brain activity (fALFF, ALFF and REHO), or that provide a parsimonious index of integrated and segregated brain activity (HE), were more broadly modulated in regions related to emotions and their regulation. Metrics related to connectivity were modulated across a wider network of areas. Overall, these results show that neuroticism affects distinct aspects of brain resting state activity. More in general, these findings indicate that a multiparametric approach may be required to obtain a more detailed characterization of the neural underpinnings of a given psychological trait.

Characterizing object- and position-dependent response profiles to uni- and bilateral stimulus configurations in human higher visual cortex: a 7T fMRI study

Visual scenes are initially processed via segregated neural pathways dedicated to either of the two visual hemifields. Although higher-order visual areas are generally believed to utilize invariant object representations (abstracted away from features such as stimulus position), recent findings suggest they retain more spatial information than previously thought.Here, we assessed the nature of such higher-order object representations in human cortex using high-resolution fMRI at 7T, supported by corroborative 3T data. We show that multi-voxel activation patterns in both the contra- and ipsilateral hemisphere can be exploited to successfully classify the object category of unilaterally presented stimuli. Moreover, robustly identified rank order-based response profiles demonstrated a strong contralateral bias which frequently outweighed object category preferences. Finally, we contrasted different combinatorial operations to predict the responses during bilateral stimulation conditions based on responses to their constituent unilateral elements. Results favored a max operation predominantly reflecting the contralateral stimuli. The current findings extend previous work by showing that configuration-dependent modulations in higher-order visual cortex responses as observed in single unit activity have a counterpart in human neural population coding. They furthermore corroborate the emerging view that position coding is a fundamental functional characteristic of ventral visual stream processing.

Modulation of locus coeruleus activity by novel oddball stimuli.

It has long been known from animal literature that the locus coeruleus (LC), the source region of noradrenergic neurons in the brain, is sensitive to unexpected, novel, and other salient events. In humans, however, direct assessment of LC activity has proven to be challenging due to its small size and difficult localization, which is why noradrenergic activity has often been assessed using more indirect measures such as electroencephalography (EEG) and pupil recordings. Here, we combined high-resolution functional magnetic resonance imaging (fMRI) with a special anatomical sequence to assess neural activity in the LC in response to different types of salient stimuli in an oddball paradigm (novel neutral oddballs, novel emotional oddballs, and familiar target oddballs). We found a significant linear increase of LC activity from standard trials, over familiar target oddballs, to novel neutral and novel emotional oddballs. Importantly, when breaking down this linear trend, only novel oddball stimuli led to robust activity increases as compared to standard trials, with no statistical difference between neutral and emotional ones. This pattern suggests that activity modulations in the LC in the present study were mainly driven by stimulus novelty, rather than by emotional saliency, task relevance, or contextual novelty alone. Moreover, the absence of significant activity modulations in response to target oddballs (which were reported in a recent study) suggests that the LC represents relative rather than absolute saliency of a stimulus in its respective context.

Dual-TRACER: High resolution fMRI with constrained evolution reconstruction

fMRI with high spatial resolution is beneficial for studies in psychology and neuroscience, but is limited by various factors such as prolonged imaging time, low signal to noise ratio and scarcity of advanced facilities. Compressed Sensing (CS) based methods for accelerating fMRI data acquisition are promising. Other advanced algorithms like k-t FOCUSS or PICCS have been developed to improve performance. This study aims to investigate a new method, Dual-TRACER, based on Temporal Resolution Acceleration with Constrained Evolution Reconstruction (TRACER), for accelerating fMRI acquisitions using golden angle variable density spiral. Both numerical simulations and in vivo experiments at 3T were conducted to evaluate and characterize this method. Results show that Dual-TRACER can provide functional images with a high spatial resolution (1×1mm2) under an acceleration factor of 20 while maintaining hemodynamic signals well. Compared with other investigated methods, dual-TRACER provides a better signal recovery, higher fMRI sensitivity and more reliable activation detection.

Linking brain vascular physiology to hemodynamic response in ultra-high field MRI

Functional MRI using blood oxygenation level-dependent (BOLD) contrast indirectly probes neuronal activity via evoked cerebral blood volume (CBV) and oxygenation changes. Thus, its spatio-temporal characteristics are determined by vascular physiology and MRI parameters. In this paper, we focus on the spatial distribution and time course of the fMRI signal and their magnetic field strength dependence. Even though much is still unknown, the following consistent picture is emerging: a) For high spatial resolution imaging, fMRI contrast-to-noise increases supra-linearly with field strength. b) The location and spacing of penetrating arteries and ascending veins in the cortical tissue are not correlated to cortical columns, imposing limitations on achievable point-spread function (PSF) in fMRI. c) Baseline CBV distribution may vary over cortical layers biasing fMRI signal to layers with high CBV values. d) The largest CBV change is in the tissue microvasculature, less in surface arteries and even less in pial veins. e) Venous CBV changes are only relevant for longer stimuli, and oxygenation changes are largest in post-capillary blood vessels. f) The balloon effect (i.e. slow recovery of CBV to baseline) is located in the tissue, consistent with the fact that the post-stimulus undershoot has narrower spatial PSF than the positive BOLD response. g) The onset time following stimulation has been found to be shortest in middle/lower layers, both in optical imaging and high-resolution fMRI, but we argue and demonstrate with simulations that varying signal latencies can also be caused by vascular properties and, therefore, may potentially not be interpreted as neural latencies. With simulations, we illustrate the field strength dependency of fMRI signal transients, such as the adaptation during stimulation, initial dip and the post-stimulus undershoot. In sum, vascular structure and function impose limitations on the achievable PSF of fMRI and give rise to complex fMRI transients, which contain time-varying amount of excitatory and inhibitory neuronal information. Nevertheless, non-invasive fMRI at ultra-high magnetic fields not only provides high contrast-to-noise but also an unprecedented detailed view on cognitive processes in the human brain.

Ultra-High-Field fMRI Reveals a Role for the Subiculum in Scene Perceptual Discrimination.

Recent “representational” accounts suggest a key role for the hippocampus in complex scene perception. Due to limitations in scanner field strength, however, the functional neuroanatomy of hippocampal-dependent scene perception is unknown. Here, we applied 7 T high-resolution functional magnetic resonance imaging (fMRI) alongside a perceptual oddity task, modified from nonhuman primate studies. This task requires subjects to discriminate highly similar scenes, faces, or objects from multiple viewpoints, and has revealed selective impairments during scene discrimination following hippocampal lesions. Region-of-interest analyses identified a preferential response in the subiculum subfield of the hippocampus during scene, but not face or object, discriminations. Notably, this effect was in the anteromedial subiculum and was not modulated by whether scenes were subsequently remembered or forgotten. These results highlight the value of ultra-high-field fMRI in generating more refined, anatomically informed, functional accounts of hippocampal contributions to cognition, and a unique role for the human subiculum in discrimination of complex scenes from different viewpoints.SIGNIFICANCE STATEMENT There is increasing evidence that the human hippocampus supports functions beyond just episodic memory, with human lesion studies suggesting a contribution to the perceptual processing of navigationally relevant, complex scenes. While the hippocampus itself contains several small, functionally distinct subfields, examining the role of these in scene processing has been previously limited by scanner field strength. By applying ultra-high-resolution 7 T fMRI, we delineated the functional contribution of individual hippocampal subfields during a perceptual discrimination task for scenes, faces, and objects. This demonstrated that the discrimination of scenes, relative to faces and objects, recruits the anterior subicular region of the hippocampus, regardless of whether scenes were subsequently remembered or forgotten.

Transformed Neural Pattern Reinstatement during Episodic Memory Retrieval.

Contemporary models of episodic memory posit that remembering involves the reenactment of encoding processes. Although encoding-retrieval similarity has been consistently reported and linked to memory success, the nature of neural pattern reinstatement is poorly understood. Using high-resolution fMRI on human subjects, our results obtained clear evidence for item-specific pattern reinstatement in the frontoparietal cortex, even when the encoding-retrieval pairs shared no perceptual similarity. No item-specific pattern reinstatement was found in the ventral visual cortex. Importantly, the brain regions and voxels carrying item-specific representation differed significantly between encoding and retrieval, and the item specificity for encoding-retrieval similarity was smaller than that for encoding or retrieval, suggesting different nature of representations between encoding and retrieval. Moreover, cross-region representational similarity analysis suggests that the encoded representation in the ventral visual cortex was reinstated in the frontoparietal cortex during retrieval. Together, these results suggest that, in addition to reinstatement of the originally encoded pattern in the brain regions that perform encoding processes, retrieval may also involve the reinstatement of a transformed representation of the encoded information. These results emphasize the constructive nature of memory retrieval that helps to serve important adaptive functions.SIGNIFICANCE STATEMENT Episodic memory enables humans to vividly reexperience past events, yet how this is achieved at the neural level is barely understood. A long-standing hypothesis posits that memory retrieval involves the faithful reinstatement of encoding-related activity. We tested this hypothesis by comparing the neural representations during encoding and retrieval. We found strong pattern reinstatement in the frontoparietal cortex, but not in the ventral visual cortex, that represents visual details. Critically, even within the same brain regions, the nature of representation during retrieval was qualitatively different from that during encoding. These results suggest that memory retrieval is not a faithful replay of past event but rather involves additional constructive processes to serve adaptive functions.

Disruption of amygdala-entorhinal-hippocampal network in late-life depression.

Episodic memory deficits are evident in late-life depression (LLD) and are associated with subtle synaptic and neurochemical changes in the medial temporal lobes (MTL). However, the particular mechanisms by which memory impairment occurs in LLD are currently unknown. We tested older adults with (DS+) and without (DS-) depressive symptoms using high-resolution fMRI that is capable of discerning signals in hippocampal subfields and amygdala nuclei. Scanning was conducted during performance of an emotional discrimination task used previously to examine the relationship between depressive symptoms and amygdala-mediated emotional modulation of hippocampal pattern separation in young adults. We found that hippocampal dentate gyrus (DG)/CA3 activity was reduced during correct discrimination of negative stimuli and increased during correct discrimination of neutral items in DS+ compared to DS- adults. The extent of the latter increase was correlated with symptom severity. Furthermore, DG/CA3 and basolateral amygdala (BLA) activity predicted discrimination performance on negative trials, a relationship that depended on symptom severity. The impact of the BLA on depressive symptom severity was mediated by the DG/CA3 during discrimination of neutral items, and by the lateral entorhinal cortex (LEC) during false recognition of positive items. These results shed light on a novel mechanistic account for amygdala-hippocampal network changes and concurrent alterations in emotional episodic memory in LLD. The BLA-LEC-DG/CA3 network, which comprises a key pathway by which emotion modulates memory, is specifically implicated in LLD. © 2017 Wiley Periodicals, Inc.

Evaluation of SLIce Dithered Enhanced Resolution Simultaneous MultiSlice (SLIDER-SMS) for human fMRI

High isotropic resolution fMRI is challenging primarily due to long repetition times (TR) and insufficient SNR, especially at lower field strengths. Recently, Simultaneous Multi-Slice (SMS) imaging with blipped-CAIPI has substantially reduced scan time and improved SNR efficiency of fMRI. Similarly, super-resolution techniques utilizing sub- voxel spatial shifts in the slice direction have increased both resolution and SNR efficiency. Here we demonstrate the synergistic combination of SLIce Dithered Enhanced Resolution (SLIDER) and SMS for high-resolution, high-SNR whole brain fMRI in comparison to standard resolution fMRI data as well as high-resolution data. With SLIDER-SMS, high spatial frequency information is recovered (unaliased) even in absence of super-resolution deblurring algorithms. Additionally we find that BOLD CNR (as measured by t-value in a visual checkerboard paradigm) is improved by as much as 100% relative to traditionally acquired high- resolution data. Using this gain in CNR, we are able to obtain unprecedented nominally isotropic resolutions at 3T (0.66 mm) and 7T (0.45 mm).

High-Resolution fMRI of Auditory Cortical Map Changes in Unilateral Hearing Loss and Tinnitus.

Animal models of hearing loss and tinnitus observe pathological neural activity in the tonotopic frequency maps of the primary auditory cortex. Here, we applied ultra high-field fMRI at 7T to test whether human patients with unilateral hearing loss and tinnitus also show altered functional activity in the primary auditory cortex. The high spatial resolution afforded by 7T imaging allowed tonotopic mapping of primary auditory cortex on an individual subject basis. Eleven patients with unilateral hearing loss and tinnitus were compared to normal-hearing controls. Patients showed an over-representation and hyperactivity in a region of the cortical map corresponding to low frequencies sounds, irrespective of the hearing loss and tinnitus range, which in most cases affected higher frequencies. This finding of hyperactivity in low frequency map regions, irrespective of hearing loss range, is consistent with some previous studies in animal models and corroborates a previous study of human tinnitus. Thus these findings contribute to accumulating evidence that gross cortical tonotopic map reorganization is not a causal factor of tinnitus.

Reliability of the depth-dependent high-resolution BOLD hemodynamic response in human visual cortex and vicinity

Functional magnetic resonance imaging (fMRI) often relies on a hemodynamic response function (HRF), the stereotypical blood oxygen level dependent (BOLD) response elicited by a brief (<4s) stimulus. Early measurements of the HRF used coarse spatial resolutions (≥3mm voxels) that would generally include contributions from white matter, gray matter, and the extra-pial compartment (the space between the pial surface and skull including pial blood vessels) within each voxel. To resolve these contributions, high-resolution fMRI (0.9-mm voxels) was performed at 3T in early visual cortex and its apposed white-matter and extra-pial compartments. The results characterized the depth dependence of the HRF and its reliability during nine fMRI sessions. Significant HRFs were observed in white-matter and extra-pial compartments as well as in gray matter. White-matter HRFs were faster and weaker than in the gray matter, while extra-pial HRFs were comparatively slower and stronger. Depth trends of the HRF peak amplitude were stable throughout a broad depth range that included all three compartments for each session. Across sessions, however, the depth trend of HRF peak amplitudes was stable only in the white matter and deep-intermediate gray matter, while there were strong session-to-session variations in the superficial gray matter and the extra-pial compartment. Thus, high-resolution fMRI can resolve significant and dynamically distinct HRFs in gray matter, white matter, and extra-pial compartments.